Effect of 3,5-di-iodo-L-thyronine on the mitochondrial energy-transduction apparatus.
We examined the effect of a single injection of 3,5-di-iodo-L-thyronine (3,5-T2) (150 microg/100 g body weight) on the rat liver mitochondrial energy-transduction apparatus. We applied 'top-down' elasticity analysis, which allows identification of the site of action of an effector within a metabolic pathway. This kinetic approach considers oxidative phosphorylation as two blocks of reactions: those generating the mitochondrial inner-membrane potential (DeltaPsi; 'substrate oxidation') and those 'consuming' it ('proton leak' and 'phosphorylating system'). The results show that 1 h after the injection of 3,5-T2, state 4 (respiratory state in which there is no ATP synthesis and the exogenous ADP added has been exhausted) and state 3 (respiratory state in which ATP synthesis is at maximal rate) of mitochondrial respiration were significantly increased (by approx. 30%). 'Top-down' elasticity analysis revealed that these increases were due to the stimulation of reactions involved in substrate oxidation; neither 'proton leak' nor the 'phosphorylating system' was influenced by 3,5-T2. Using the same approach we divided the respiratory chain into two blocks of reactions: cytochrome c reducers and cytochrome c oxidizers. We found that both cytochrome c reducers and cytochrome c oxidizers are targets for 3,5-T2. The rapidity with which 3,5-T2 acts in stimulating the mitochondrial respiration rate suggests to us that di-iodo-L-thyronine may play an important role in the physiological conditions in which rapid energy utilization is required, such as cold exposure or overfeeding.
Lombardi
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A
Dipartimento di Fisiologia Generale ed Ambientale, Università di Napoli 'Federico II', Via Mezzocannone, 8, 80134 Napoli, Italy.
Lanni
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A
Moreno
M
M
Brand
M D
MD
Goglia
F
F
D000818:Animals; D003574:Cytochrome c Group / Q000378:metabolism; D004104:Diiodothyronines / Q000494:pharmacology*; D004734:Energy Metabolism / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D010084:Oxidation-Reduction; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
D003574:Cytochrome c Group; D004104:Diiodothyronines; C030103:3,5-diiodothyronine